{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:32:44Z","timestamp":1793446364170,"version":"4.5.0"},"reference-count":51,"publisher":"Radiation Research Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2020,8,3]]},"abstract":"<jats:p>Persistent vasculature abnormalities contribute to an altered CNS microenvironment that further compromises the integrity of the blood-brain barrier and exposes the brain to a host of neurotoxic conditions. Standard radiation therapy at conventional (CONV) dose rate elicits short-term damage to the blood-brain barrier by disrupting supportive cells, vasculature volume and tight junction proteins. While current clinical applications of cranial radiotherapy use dose fractionation to reduce normal tissue damage, these treatments still cause significant complications. While dose escalation enhances treatment of radiation-resistant tumors, methods to subvert normal tissue damage are clearly needed. In this regard, we have recently developed a new modality of irradiation based on the use of ultra-high-dose-rate FLASH that does not induce the classical pathogenic patterns caused by CONV irradiation. In previous work, we optimized the physical parameters required to minimize normal brain toxicity (i.e., FLASH, instantaneous intra-pulse dose rate, 6.9 \u00b7 106 Gy\/s, at a mean dose rate of 2,500 Gy\/s), which we then used in the current study to determine the effect of FLASH on the integrity of the vasculature and the blood-brain barrier. Both early (24 h, one week) and late (one month) timepoints postirradiation were investigated using C57Bl\/6J female mice exposed to whole-brain irradiation delivered in single doses of 25 Gy and 10 Gy, respectively, using CONV (0.09 Gy\/s) or FLASH (&gt;106 Gy\/s). While the majority of changes found one day postirradiation were minimal, FLASH was found to reduce levels of apoptosis in the neurogenic regions of the brain at this time. At one week and one month postirradiation, CONV was found to induce vascular dilation, a well described sign of vascular alteration, while FLASH minimized these effects. These results were positively correlated with and temporally coincident to changes in the immunostaining of the vasodilator eNOS colocalized to the vasculature, suggestive of possible dysregulation in blood flow at these latter times. Overall expression of the tight junction proteins, occludin and claudin-5, which was significantly reduced after CONV irradiation, remained unchanged in the FLASH-irradiated brains at one and four weeks postirradiation. Our data further confirm that, compared to isodoses of CONV irradiation known to elicit detrimental effects, FLASH does not damage the normal vasculature. These data now provide the first evidence that FLASH preserves microvasculature integrity in the brain, which may prove beneficial to cognition while allowing for better tumor control in the clinic.<\/jats:p>","DOI":"10.1667\/rade-20-00060.1","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T09:15:46Z","timestamp":1649063746000},"page":"625-635","source":"Crossref","is-referenced-by-count":68,"title":["Maintenance of Tight Junction Integrity in the Absence of Vascular Dilation in the Brain of Mice Exposed to Ultra-High-Dose-Rate FLASH Irradiation"],"prefix":"10.1667","volume":"194","author":[{"given":"Barrett D.","family":"Allen","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of California, Irvine, Irvine, California 92697-2695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munjal M.","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California, Irvine, Irvine, California 92697-2695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Montay-Gruel","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Oncology, Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik Goncalves","family":"Jorge","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Oncology, Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Bailat","sequence":"additional","affiliation":[{"name":"Institute of Radiation Physics\/CHUV, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Petit","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Oncology, Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Catherine","family":"Vozenin","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Oncology, Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Limoli","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California, Irvine, Irvine, California 92697-2695"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"39","doi-asserted-by":"crossref","unstructured":"HS Reinhold, W Calvo, 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Shaw,  \"Curr Treat Options Oncol.\"  7, \"Managing the cognitive effects of brain tumor radiation therapy.\" 517 (2006)","DOI":"10.1007\/s11864-006-0026-5"},{"key":"36","doi-asserted-by":"crossref","unstructured":"DA Simmons, FM Lartey, E Schuler, et al.  \"Radiother Oncol.\"  139, \"Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation.\" 4 (2019)","DOI":"10.1016\/j.radonc.2019.06.006"},{"key":"9","doi-asserted-by":"crossref","unstructured":"D Roongpiboonsopit, HJ Kuijf, A Charidimou, et al.  \"Neurology.\"  88, \"Evolution of cerebral microbleeds after cranial irradiation in medulloblastoma patients.\" 789 (2017)","DOI":"10.1212\/WNL.0000000000003631"},{"key":"22","doi-asserted-by":"crossref","unstructured":"MC Vozenin, P De Fornel, K Petersson, et al.  \"Clin Cancer Res.\"  25, \"The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients.\" 35 (2019)","DOI":"10.1158\/1078-0432.CCR-17-3375"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:05:43Z","timestamp":1793444743000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-194\/issue-6\/RADE-20-00060.1\/Maintenance-of-Tight-Junction-Integrity-in-the-Absence-of-Vascular\/10.1667\/RADE-20-00060.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,3]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,12,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-20-00060.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,3]]}}}